The study of innate drug resistance of human hepatocellular carcinoma Bel(7402) cell line

The innate drug resistance of human hepatocellular carcinoma (HCC) Bel(7402 ) cell line was studied in vitro. MTT assay showed that Bel(7402) cells wer e innately resistant to doxorubicin (Dox), and even more resistant to vincr istine (VCR). This resistance could be effectively reversed by verapamil (V er), one of the classical multidrug resistance (MDR) modulating agents. How ever, the differences in 5-fluorouracil (5-FU) toxicity between these two c ell lines is much less and the resistance of Bel(7402) cells could only be slightly reversed by Ver, which may be experimental noise. Immunocytochemic al staining using anti-p-glycoprotein monoclonal antibody JSB-1 indicated t hat the expression of the P-glycoprotein (P-gp) in the innate Bel(7402) cel ls was elevated compared with the sensitive KB cells. The accumulation of D ox in innate resistant Bel(7402) cells was 50.7% lower than that in sensiti ve KB cells by using spectrofluometric analyses, and the accumulation of Do x increased 1.6 fold in Bel(7402) cells in the presence of Ver. The suscept ibility of Dox-induced apoptosis was also increased in the presence of Ver by using flow cytometric assay and DNA fragmentation quantitative assay as well as by Hoechst 33258 staining. It appears that the innate Bel(7402) cel ls might be useful in screening new antitumour drugs or new chemosensitiser s which could overcome the innate or acquired resistant mechanism, and the toxicity and reversal effects with 5-FU are different from those known to b e P-gp substrates such as VCR; Dox, and taxol. (C) 1999 Elsevier Science Ir eland Ltd. All rights reserved.